IL-2 and IL-15 Receptor Alpha-subunits Are Coexpressed in a Supramolecular Receptor Cluster in Lipid Rafts of T Cells

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2004 Jul 21

PMID 15263076

Citations 47

Authors

Gyorgy Vamosi

Andrea Bodnar

Gyorgy Vereb

Attila Jenei

Carolyn K Goldman

Jorg Langowski

Katalin Toth

Laszlo Matyus

Janos Szollosi

Thomas A Waldmann

Sandor Damjanovich

Affiliations

Soon will be listed here.

Abstract

The private alpha-chains of IL-2 and IL-15 receptors (IL-2R and IL-15R) share the signaling beta- and gamma(c)-subunits, resulting in both common and contrasting roles of IL-2 and IL-15 in T cell function. Knowledge of the cytokine-dependent subunit assembly is indispensable for understanding the paradox of distinct signaling capacities. By using fluorescence resonance energy transfer and confocal microscopy, we have shown that IL-2R alpha, IL-15R alpha, IL-2/15R beta and gamma(c)-subunits, as well as MHC class I and II glycoproteins formed supramolecular receptor clusters in lipid rafts of the T lymphoma line Kit 225 FT7.10. Fluorescence crosscorrelation microscopy demonstrated the comobility of IL-15R alpha with IL-2R alpha and MHC class I. A model was generated for subunit switching between IL-2R alpha and IL-15R alpha upon the binding of the appropriate cytokine resulting in the formation of high-affinity heterotrimeric receptors. This model suggests a direct role for the alpha-subunits, to which no definite function has been assigned so far, in tuning cellular responses to IL-2 or IL-15. In addition, both alpha-chains were at least partially homodimerized/oligomerized, which could be the basis of distinct signaling pathways by the two cytokines.

Citing Articles

Arachidonic acid impairs natural killer cell functions by disrupting signaling pathways driven by activating receptors and reactive oxygen species.

Hammoud M, Meena C, Dietze R, Hoffmann N, Szymanski W, Finkernagel F Cell Commun Signal. 2024; 22(1):555.

PMID: 39563446 PMC: 11575453. DOI: 10.1186/s12964-024-01940-z.

Nucleotide binding is the critical regulator of ABCG2 conformational transitions.

Gyongy Z, Mocsar G, Hegedus E, Stockner T, Ritter Z, Homolya L Elife. 2023; 12.

PMID: 36763413 PMC: 9917445. DOI: 10.7554/eLife.83976.

Reduced Serum Levels of Soluble Interleukin-15 Receptor α in Schizophrenia and Its Relationship to the Excited Phenotype.

He Y, Bo Q, Mao Z, Yang J, Liu M, Wang H Front Psychiatry. 2022; 13:842003.

PMID: 35356722 PMC: 8959406. DOI: 10.3389/fpsyt.2022.842003.

Role of C-Terminal Domain and Membrane Potential in the Mobility of Kv1.3 Channels in Immune Synapse Forming T Cells.

Sebestyen V, Nagy E, Mocsar G, Volko J, Szilagyi O, Kenesei A Int J Mol Sci. 2022; 23(6).

PMID: 35328733 PMC: 8952507. DOI: 10.3390/ijms23063313.

IL-15 -Presentation Is an Autonomous, Antigen-Independent Process.

Kenesei A, Volko J, Szaloki N, Mocsar G, Jambrovics K, Balajthy Z J Immunol. 2021; 207(10):2489-2500.

PMID: 34654688 PMC: 8578424. DOI: 10.4049/jimmunol.2100277.

References

Medina M, Schwille P . Fluorescence correlation spectroscopy for the detection and study of single molecules in biology. Bioessays. 2002; 24(8):758-64. DOI: 10.1002/bies.10118. View

Dubois S, Shou W, Haneline L, Fleischer S, Waldmann T, Muller J . Distinct pathways involving the FK506-binding proteins 12 and 12.6 underlie IL-2-versus IL-15-mediated proliferation of T cells. Proc Natl Acad Sci U S A. 2003; 100(24):14169-74. PMC: 283564. DOI: 10.1073/pnas.2335979100. View

Oh S, Berzofsky J, Burke D, Waldmann T, Perera L . Coadministration of HIV vaccine vectors with vaccinia viruses expressing IL-15 but not IL-2 induces long-lasting cellular immunity. Proc Natl Acad Sci U S A. 2003; 100(6):3392-7. PMC: 152303. DOI: 10.1073/pnas.0630592100. View

Dubois S, Mariner J, Waldmann T, Tagaya Y . IL-15Ralpha recycles and presents IL-15 In trans to neighboring cells. Immunity. 2002; 17(5):537-47. DOI: 10.1016/s1074-7613(02)00429-6. View

Waldmann T, Dubois S, Tagaya Y . Contrasting roles of IL-2 and IL-15 in the life and death of lymphocytes: implications for immunotherapy. Immunity. 2001; 14(2):105-10. View

Bulanova E, Budagian V, Pohl T, Krause H, Durkop H, Paus R . The IL-15R alpha chain signals through association with Syk in human B cells. J Immunol. 2001; 167(11):6292-302. DOI: 10.4049/jimmunol.167.11.6292. View

Szentesi G, Horvath G, Bori I, Vamosi G, Szollosi J, Gaspar R . Computer program for determining fluorescence resonance energy transfer efficiency from flow cytometric data on a cell-by-cell basis. Comput Methods Programs Biomed. 2004; 75(3):201-11. DOI: 10.1016/j.cmpb.2004.02.004. View

Szollosi J, Horejsi V, Bene L, Angelisova P, Damjanovich S . Supramolecular complexes of MHC class I, MHC class II, CD20, and tetraspan molecules (CD53, CD81, and CD82) at the surface of a B cell line JY. J Immunol. 1996; 157(7):2939-46. View

Harder T, Scheiffele P, Verkade P, Simons K . Lipid domain structure of the plasma membrane revealed by patching of membrane components. J Cell Biol. 1998; 141(4):929-42. PMC: 2132776. DOI: 10.1083/jcb.141.4.929. View

10.

Magde D, Elson E, Webb W . Fluorescence correlation spectroscopy. II. An experimental realization. Biopolymers. 1974; 13(1):29-61. DOI: 10.1002/bip.1974.360130103. View

11.

Nakamura Y, Russell S, Mess S, Friedmann M, Erdos M, Francois C . Heterodimerization of the IL-2 receptor beta- and gamma-chain cytoplasmic domains is required for signalling. Nature. 1994; 369(6478):330-3. DOI: 10.1038/369330a0. View

12.

Stryer L, Haugland R . Energy transfer: a spectroscopic ruler. Proc Natl Acad Sci U S A. 1967; 58(2):719-26. PMC: 335693. DOI: 10.1073/pnas.58.2.719. View

13.

Wachsmuth M, Weidemann T, Muller G, Hoffmann-Rohrer U, Knoch T, Waldeck W . Analyzing intracellular binding and diffusion with continuous fluorescence photobleaching. Biophys J. 2003; 84(5):3353-63. PMC: 1302895. DOI: 10.1016/S0006-3495(03)70059-9. View

14.

Eicher D, Damjanovich S, Waldmann T . Oligomerization of IL-2Ralpha. Cytokine. 2002; 17(2):82-90. DOI: 10.1006/cyto.2001.0978. View

15.

Lin J, Migone T, Tsang M, Friedmann M, Weatherbee J, Zhou L . The role of shared receptor motifs and common Stat proteins in the generation of cytokine pleiotropy and redundancy by IL-2, IL-4, IL-7, IL-13, and IL-15. Immunity. 1995; 2(4):331-9. DOI: 10.1016/1074-7613(95)90141-8. View

16.

Bene L, Balazs M, Matko J, Most J, Dierich M, Szollosi J . Lateral organization of the ICAM-1 molecule at the surface of human lymphoblasts: a possible model for its co-distribution with the IL-2 receptor, class I and class II HLA molecules. Eur J Immunol. 1994; 24(9):2115-23. DOI: 10.1002/eji.1830240928. View

17.

Fehniger T, Caligiuri M . Interleukin 15: biology and relevance to human disease. Blood. 2001; 97(1):14-32. DOI: 10.1182/blood.v97.1.14. View

18.

Bastiaens P, Majoul I, Verveer P, SOLING H, Jovin T . Imaging the intracellular trafficking and state of the AB5 quaternary structure of cholera toxin. EMBO J. 1996; 15(16):4246-53. PMC: 452150. View

19.

Tagaya Y, Bamford R, DeFilippis A, Waldmann T . IL-15: a pleiotropic cytokine with diverse receptor/signaling pathways whose expression is controlled at multiple levels. Immunity. 1996; 4(4):329-36. DOI: 10.1016/s1074-7613(00)80246-0. View

20.

Nelson B, Willerford D . Biology of the interleukin-2 receptor. Adv Immunol. 1998; 70:1-81. DOI: 10.1016/s0065-2776(08)60386-7. View